Project Summary ? Neuropharmacology Core The Neuropharmacology Core is a new core that proposes to serve NIH-funded investigators affiliated with the P30 grant by increasing their access to key neurochemical and behavioral methodologies that are fundamental to advancement of preclinical drug abuse research. These methodologies will include techniques to assess expression and function of receptors in both tissue homogenates and tissue slices, in vivo microdialysis techniques to assess neurotransmitter levels in target brain areas in awake and behaving animals, and behavioral techniques to assess rewarding/reinforcing effects of drugs under different physiological or environmental conditions. Although this is a new core, the investigators have decades of expertise in their respective areas and a history of collaboration both with each other and with other VCU investigators. The rationale for this core is founded on the proposition that drugs of abuse act on molecular targets to modulate activity in brain reward systems and alter behavior, and preclinical drug abuse research benefits from coordinated investigation of drug effects along the entire continuum from molecular to behavioral levels of analysis. However, individual grants typically focus on a portion of this continuum and often lack resources for rapid and rational extension of important findings to other, related research domains. As one example, a synthetic chemistry grant might identify a new molecular entity with promising analgesic effects but lack resources for preclinical assessment of that compound's abuse liability or potential utility as a treatment for substance use disorders. As another example, a grant focused on behavioral studies to treat drug abuse might identify an effective medication strategy but lack resources to investigate candidate mechanisms that underlie medication efficacy. The Neuropharmacology Core proposes to address these gaps and strengthen the breadth and impact of drug abuse research at VCU. Studies of receptor expression and function (Aim 1), in vivo microdialysis (Aim 2), and behavioral expression of reward/reinforcement (Aim 3) will enable investigators to evaluate effects of pathological states or of acute/chronic drug treatments on neural systems and behavioral endpoints known to be important in drug abuse.